Govada Lata, Carpenter Liz, da Fonseca Paula C A, Helliwell John R, Rizkallah Pierre, Flashman Emily, Chayen Naomi E, Redwood Charles, Squire John M
Biomolecular Medicine Department, SORA Division, Imperial College London, London SW7 2AZ, UK.
J Mol Biol. 2008 Apr 25;378(2):387-97. doi: 10.1016/j.jmb.2008.02.044. Epub 2008 Mar 4.
C-protein is a major component of skeletal and cardiac muscle thick filaments. Mutations in the gene encoding cardiac C-protein [cardiac myosin binding protein-C (cMyBP-C)] are one of the principal causes of hypertrophic cardiomyopathy. cMyBP-C is a string of globular domains including eight immunoglobulin-like and three fibronectin-like domains termed C0-C10. It binds to myosin and titin, and probably to actin, and may have both a structural and a regulatory role in muscle function. To help to understand the pathology of the known mutations, we have solved the structure of the immunoglobulin-like C1 domain of MyBP-C by X-ray crystallography to a resolution of 1.55 A. Mutations associated with hypertrophic cardiomyopathy are clustered at one end towards the C-terminus, close to the important C1C2 linker, where they alter the structural integrity of this region and its interactions.
C蛋白是骨骼肌和心肌粗肌丝的主要成分。编码心脏C蛋白[心肌肌球蛋白结合蛋白-C（cMyBP-C）]的基因突变是肥厚型心肌病的主要病因之一。cMyBP-C是一串球状结构域，包括八个免疫球蛋白样结构域和三个纤连蛋白样结构域，分别称为C0-C10。它与肌球蛋白和肌联蛋白结合，可能还与肌动蛋白结合，并且可能在肌肉功能中兼具结构和调节作用。为了帮助理解已知突变的病理机制，我们通过X射线晶体学解析了MyBP-C免疫球蛋白样C1结构域的结构，分辨率达到1.55埃。与肥厚型心肌病相关的突变集中在靠近C末端的一端，靠近重要的C1C2连接区，这些突变改变了该区域的结构完整性及其相互作用。
